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Background Relapse of depression is common and contributes to the overall associated morbidity and burden. We lack evidence-based tools to estimate an individual’s risk of relapse after treatment in primary care, which may help us more effectively target relapse prevention.Objective The objective was to develop and validate a prognostic model to predict risk of relapse of depression in primary care.Methods Multilevel logistic regression models were developed, using individual participant data from seven primary care-based studies (n=1244), to predict relapse of depression. The model was internally validated using bootstrapping, and generalisability was explored using internal–external cross-validation.Findings Residual depressive symptoms (OR: 1.13 (95% CI: 1.07 to 1.20), p

Background The COVID-19 pandemic initiated a mass switch to psychological therapy being delivered remotely, including at Anxiety UK, a national mental health charity. Understanding the impact of this forced switch could raise implications for the provision of psychological therapies going forwards. Aims To understand whether the forced switch to remote therapy had any impact on outcomes, and if certain groups should continue to be routinely offered certain delivery modalities in future. Method Data were available for 2323 individuals who accessed Anxiety UK services between January 2019 and October 2021. Demographic data, baseline and discharge anxiety and depression symptoms, and mode of therapy delivery were available. Regression models were built to model (a) the mode of therapy delivery received pre-pandemic using logistic regression, and (b) outcomes pre- and post-pandemic onset within demographic groups. Results No statistically significant changes in baseline anxiety symptoms, demographics or outcomes were observed before and after the onset of the COVID-19 pandemic. Pre-pandemic, males were more likely to receive online video therapy than telephone therapy (Relative Risk Ratio (RRR) 1.42, [1.01, 1.99]), while older clients were less likely to receive online video therapy (RRR 0.98, [0.97, 0.99]). However, no differences in outcomes were observed post-pandemic onset within these groups, with only the number of sessions of therapy being a significant predictor of outcomes. Conclusions Anxiety UK services remained effective throughout the pandemic. We observed no evidence that any demographic group had worse outcomes following the forced switch to remote therapy.

Abstract Gastrointestinal (GI) disruptions and inflammatory bowel disease (IBD) are commonly associated with Parkinson’s disease (PD), but how they may impact risk for PD remains poorly understood. Herein, we provide evidence that prodromal intestinal inflammation expedites and exacerbates PD endophenotypes in rodent carriers of the human PD risk allele LRRK2 G2019S in a sex-dependent manner. Chronic intestinal damage in genetically predisposed male mice promotes α-synuclein aggregation in the substantia nigra, loss of dopaminergic neurons and motor impairment. This male bias is preserved in gonadectomized males, and similarly conferred by sex chromosomal complement in gonadal females expressing human LRRK2 G2019S. The early onset and heightened severity of neuropathological and behavioral outcomes in male LRRK2 G2019S mice is preceded by increases in α-synuclein in the colon, α-synuclein-positive macrophages in the colonic lamina propria, and loads of phosphorylated α-synuclein within microglia in the substantia nigra. Taken together, these data reveal that prodromal intestinal inflammation promotes the pathogenesis of PD endophenotypes in male carriers of LRRK2 G2019S, through mechanisms that depend on genotypic sex and involve early accumulation of α-synuclein in myeloid cells within the gut.

Background: Regulations restricting the promotion of some less-healthy products high in fat, sugar, or salt (HFSS) within “restricted areas” (RAs) of supermarkets came into force in October 2022 in England. Objectives: To evaluate the prevalence of HFSS products and front-of-pack nutrition labeling (FOPNL) characteristics of foods sold within RAs in a sample of supermarket stores. Methods: A cross-sectional survey of products in RAs in 3 supermarkets was undertaken from November 2022 to February 2023 using photographs, recording the display of FOPNL. Identified via the online supermarket, product nutrition and ingredient data were collected and used to categorize each as either “in” or out-of-scope of the regulations. The UK Nutrient Profiling Model was used to determine product HFSS status and the FOPNL multiple traffic light criteria used to calculate the number of inherent red traffic lights (iRTLs) possessed. Prevalence of HFSS, FOPNL, and iRTLs were calculated as a proportion (%) of total products. Associations between these characteristics were explored using chi-squared tests. Results: A total of 86 RAs were identified across the 3 stores, of which 32 displayed 679 food products. Most of these products fell into categories considered out-of-scope of the regulations (64%, n = 435) with prevalence of HFSS at 42% (282 of 435 products). For products within in-scope categories, 17% were HFSS (42 of 245). Half of all included products (53%, n = 357) displayed FOPNL, and 16% possessed 1–3 iRTLs, including both HFSS and non-HFSS items. HFSS products in categories in-scope of the regulations were less likely to display FOPNL compared with non-HFSS products (X2 =25, P < 0.001). Conclusions: After the implementation of The Food (Promotion and Placement) Regulations, foods sold in RAs of 3 supermarkets included those in categories in- and out-of-scope, a variable prevalence of less-healthy (HFSS) products, display of FOPNL, and possession of iRTLs. Findings and approach support future impact evaluation.

Background: Selection into UK-based GP training has used the Multi-Specialty Recruitment Assessment (MSRA) and a face-to-face selection centre (SC). The MSRA comprises of a situational judgement test and clinical problem-solving test. The SC was suspended during the COVID-19 pandemic. Evidence is needed to guide national and international selection policy. Aim: To evaluate the validity of GP training selection. Design & setting: A retrospective cohort study using data from UK-based national recruitment to GP training, from 2015–2021. Method: Data were available for 32 215 GP training applicants. The ability of scores from the specialty selection process to predict subsequent performance in the Clinical Skills Assessment (CSA) of the Membership of the Royal College of General Practitioners examination was modelled using path analysis. The effect sizes for sex, professional family background, and world region of qualification were estimated. Results: All component scores of the selection process demonstrated statistically significant independent relationships with CSA performance (P

Decidualisation, the process whereby endometrial stromal cells undergo morphological and functional transformation in preparation for trophoblast invasion, is often disrupted in women with polycystic ovary syndrome (PCOS) resulting in complications with pregnancy and/or infertility. The transcription factor Wilms tumour suppressor 1 (WT1) is a key regulator of the decidualization process, which is reduced in patients with PCOS, a complex condition characterized by increased expression of androgen receptor in endometrial cells and high presence of circulating androgens. Using genome-wide chromatin immunoprecipitation approaches on primary human endometrial stromal cells, we identify key genes regulated by WT1 during decidualization, including homeobox transcription factors which are important for regulating cell differentiation. Furthermore, we found that AR in PCOS patients binds to the same DNA regions as WT1 in samples from healthy endometrium, suggesting dysregulation of genes important to decidualisation pathways in PCOS endometrium due to competitive binding between WT1 and AR. Integrating RNA-seq and H3K4me3 and H3K27ac ChIP-seq metadata with our WT1/AR data, we identified a number of key genes involved in immune response and angiogenesis pathways that are dysregulated in PCOS patients. This is likely due to epigenetic alterations at distal enhancer regions allowing AR to recruit cofactors such as MAGEA11, and demonstrates the consequences of AR disruption of WT1 in PCOS endometrium.

ABSTRACTHistoplasma capsulatum var. farciminosum (HCF) is a dimorphic fungus that causes epizootic lymphangitis in equids. Current diagnostic approaches, including culture, microscopy, and clinical presentation, lack speed, sensitivity, and specificity when diagnosing clinical cases. In this study, equine blood and pus samples on Whatman FTA cards from Senegal (n = 3), The Gambia (n = 19), Ethiopia (n = 16), and Mali (n = 13) were tested using a real-time PCR (qPCR) protocol. The assay was optimized and tested for its suitability to detect and quantify HCF in blood and pus loaded onto Whatman FTA cards at sampling. Whatman FTA cards were tested for their suitability for use with qPCR and were found to recover DNA more efficiently than from direct extraction. Using TaqMan fluorescent probes and specific primers, the assay demonstrated 100% analytical specificity when detecting multiple strains of Histoplasma and no false positives with off-target organisms. The assay’s diagnostic performance was measured against an existing nested internal transcribed spacer PCR protocol using a receiver operating characteristic curve. The test was found to have a diagnostic specificity and sensitivity of 100% and 71.4%, respectively, when analyzing pus samples using a cycle threshold (Ct) cutoff determined by Youden’s index (27.75). Blood sample cutoff Ct value was proposed at 34.55. Further optimization is required to improve the performance of the protocol when applied to blood samples. This study has, for the first time, demonstrated the ability to detect and quantify the DNA of Histoplasma spp. in equine blood and pus samples with a high degree of accuracy, providing a platform to further investigate the pathogenesis and epidemiology of this disease.IMPORTANCEHistoplasmosis is a neglected yet major cause of morbidity and mortality in both equids and people in resource-scarce settings. One of the major hindrances to the control of histoplasmosis is a lack of readily available diagnostic tests. Tests are needed to support clinical decision-making and to be applied in population-based research to further understand this disease in situ. This paper reports, for the first time, the validation and application of a qPCR to detect Histoplasma directly from equine clinical samples, bypassing the need to culture this notoriously difficult organism. We report and comment on the performance of the qPCR in comparison with our previously developed nested PCR.

Abstract Objective: To evaluate the prevalence of ‘High Fat Sugar Salt’ (HFSS) products and front-of-pack nutrition labelling (FOPNL) characteristics across promoted products in UK online supermarkets. Design: A cross-sectional survey conducted (December 2021–January 2022) on promoted products. Data on ingredients, nutritional composition and display of FOPNL were collected from product webpages. The UK’s Nutrient Profiling Model and Multiple Traffic Light criteria were used to determine HFSS status and possession of inherent red traffic lights (iRTL), respectively. Data analysis determined the prevalence (i.e. percentage of products of the total number of products sampled) of HFSS; FOPNL and possession of iRTL. Chi-squared tests explored associations between these. Setting: Three major UK online supermarket retailer websites. Participants: Product ‘multibuy’ and ‘entrance’ promotions, from selected product categories. Results: Among the sampled 625 promoted products, the prevalence of HFSS was greater in entrance (73 %) compared with multibuy (41 %) promotions (χ2 (1) = 34, P < 0·05), with variations in the former across retailers (49–92 %). The prevalence of HFSS products in multibuy promotions offered by two retailers varied by category (i.e. Confectionery 94–97 %, Yogurts 20–20 %, Soft Drinks 16–33 %, Ready Meals 1·4–18 %). Not all promoted products displayed FOPNL on webpages (70 %) or images (52 %). A number of iRTL were found to be possessed by both HFSS and non-HFSS-promoted products. Conclusions: Prior to the 2022 implementation of Regulations restricting these, HFSS products were promoted in online supermarkets with varying display of FOPNL and possession of iRTL. Findings support future policy evaluation and mandatory digital FOPNL.